MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

Katsuhiro Yoshimura, MD, PhD; Yusuke Inoue, MD, PhD; Naoki Inui, MD, PhD; Masato Karayama, MD, PhD; Hideki Yasui, MD, PhD; Hironao Hozumi, MD, PhD; Yuzo Suzuki, MD, PhD; Kazuki Furuhashi, MD, PhD; Tomoyuki Fujisawa, MD, PhD; Noriyuki Enomoto, MD, PhD; Yutaro Nakamura, MD, PhD; Haruhiko Sugimura, MD, PhD; Takafumi Suda, MD, PhD

JTO Clinical and Research Reports (Nov 2021)

MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

Katsuhiro Yoshimura, MD, PhD,
Yusuke Inoue, MD, PhD,
Naoki Inui, MD, PhD,
Masato Karayama, MD, PhD,
Hideki Yasui, MD, PhD,
Hironao Hozumi, MD, PhD,
Yuzo Suzuki, MD, PhD,
Kazuki Furuhashi, MD, PhD,
Tomoyuki Fujisawa, MD, PhD,
Noriyuki Enomoto, MD, PhD,
Yutaro Nakamura, MD, PhD,
Haruhiko Sugimura, MD, PhD,
Takafumi Suda, MD, PhD

Affiliations

Katsuhiro Yoshimura, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Yusuke Inoue, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan
Naoki Inui, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan; Corresponding author. Address for correspondence: Naoki Inui, MD, PhD, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
Masato Karayama, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Hideki Yasui, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Hironao Hozumi, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Yuzo Suzuki, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Kazuki Furuhashi, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Tomoyuki Fujisawa, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Noriyuki Enomoto, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Yutaro Nakamura, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Haruhiko Sugimura, MD, PhD: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Takafumi Suda, MD, PhD: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Journal volume & issue: Vol. 2, no. 11
p. 100239

Abstract

Read online

Introduction: MET amplification is an important genetic alteration in NSCLC. Unlike in patients with EGFR and ALK alterations, the efficacy of immune checkpoint inhibitors in patients with MET-amplified NSCLC remains unknown. Methods: An exploratory analysis of a prospective, multi-institutional cohort comprising 200 patients with advanced or recurrent NSCLC treated with nivolumab monotherapy was performed, and MET amplification was defined as a MET-to-CEP7 ratio of greater than or equal to 2 using fluorescent in situ hybridization. High-level and low-level MET gains were also defined as MET signals ≥10/nuclei and 10> MET signals ≥5/nuclei, respectively. Overall response rates (ORRs) and survival outcomes were evaluated on the basis of the MET gene copy number status. Results: Among 175 patients eligible for analysis, MET amplification was detected in 13 tumors (7.4%). Four (2.3%) high-level and 14 (8.0%) low-level MET gains were also detected. There were no considerable differences in ORRs in accordance with the MET gene copy number status. Similarly, no significant differences in both progression-free survival (PFS) and overall survival (OS) were observed between patients with and without MET-amplified NSCLC (log-rank, p = 0.813 for PFS, and p = 0.855 for OS). Among 101 adenocarcinomas, ORRs in patients with high-level and low-level MET gains (50.0% for both, p = 0.049) were significantly higher than those without MET gains (17.6%), yet survival outcomes for both PFS and OS did not improve. Conclusions: MET amplification was not associated with greater benefit of nivolumab treatment in patients with NSCLC. Further studies are warranted to prioritize immune checkpoint inhibitors in the treatment regimen for patients with MET amplification.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

About the journal

Abstract

Keywords